1,2,4-oxadiazol-5-one-4-(benzimidazolylmethylamino)benzamidine compounds

Abstract

A process for preparing an optionally substituted 4-benzimidazol-2-ylmethylamino)benzamidine, the process comprising: (a) condensing an optionally suitably substituted diaminobenzene with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid; (b) hydrogenating the product obtained from step (a); and (c) optionally carboxylating the amidino group of the product obtained from step (b).

1. A compound of formula (III) 
       
         
           
           
               
               
           
         
       
       wherein: 
       R 1  is a C 1-6 -alkyl or C 3-7 -cycloalkyl group; and 
       R 2  is
 (i) a C 1-6 -alkyl group or a C 3-7 -cycloalkyl group optionally substituted by a C 1-3 -alkyl group, wherein the C 1-3 -alkyl group is optionally substituted by a carboxyl group or 
 (ii) an R 21 NR 22  group, wherein:
 R 21  is a C 1-6  alkyl group optionally substituted by a carboxy, C 1-6  alkoxycarbonyl, benzyloxycarbonyl, C 1-3 -alkylsulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, trifluorosulfonylamino, trifluorosulfonylaminocarbonyl, or 1H-tetrazolyl group, a C 2-4 -alkyl group substituted by a hydroxy, phenyl-C 1-3 -alkoxy, carboxy-C 1-3 -alkylamino, C 1-3 -alkoxycarbonyl-C 1-3 -alkylamino, N-(C 1-3 -alkyl)-carboxy-C 1-3 -alkylamino, or N-(C 1-3 -alkyl)-C 1-3 -alkoxycarbonyl-C 1-3 -alkylamino group, wherein the α-carbon atom to the adjacent nitrogen atom thereof is not substituted, or a piperidinyl group optionally substituted by a C 1-3 -alkyl group, and 
 R 22  is a hydrogen atom,
 a C 1-6 -alkyl group, 
 a C 3-7 -cycloalkyl group optionally substituted by a C 1-3 -alkyl group, 
 a C 3-6 -alkenyl, or C 3-6 -alkynyl group, wherein an unsaturated moiety of the C 3-6 -alkenyl or C 3-6 -alkynyl group is not linked directly to the nitrogen atom of the R 21 NR 22  group, 
 a phenyl group optionally substituted by a fluorine, chlorine, or bromine atom or by a C 1-3 -alkyl or C 1-3 -alkoxy group, or 
 a benzyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, or imidazolyl group optionally substituted by a C 1-3 -alkyl group; or 
 
 R 21  and R 22  together with the nitrogen atom between them are a 5- to 7-membered cycloalkyleneimino group optionally substituted by a carboxy or C 1-4 -alkoxycarbonyl group, to which a phenyl ring is optionally additionally fused. 
 
 
     
     
       2. The compound of formula (III) according to  claim 1 , wherein: 
       R 1  is a C 1-3 -alkyl group; and 
       R 2  is an R 21 NR 22  group, wherein:
 R 21  is a C 1-3  alkyl group optionally substituted by a carboxy or C 1-3  alkoxycarbonyl, and 
 R 22  is a hydrogen atom, a C 1-3 -alkyl group, or a pyridyl group optionally substituted by a C 1-3 -alkyl group. 
 
     
     
       3. The compound of formula (III) according to  claim 2 , wherein: 
       R 1  is a methyl group; 
       R 2  is an R 21 NR 22  group, wherein:
 R 21  is an ethyl group substituted by an ethoxycarbonyl group, and 
 R 22  is a pyridin-2-yl group. 
 
     
     
       4. 2-[4-(1,2,4-Oxadiazol-5-one-3-yl)phenylamino]acetic acid.